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Article Open Access

MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation

  • Authors:
    • Saed A. Althobaiti
  • View Affiliations / Copyright

    Affiliations: Department of Biology, Turabah University College, Taif University, Turabah, Taif, Mecca 21995, Saudi Arabia
    Copyright: © Althobaiti et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 296
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    Published online on: August 22, 2025
       https://doi.org/10.3892/mmr.2025.13661
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Abstract

Malathion, a commonly used organophosphate pesticide, induces severe hepatorenal toxicity, mitochondrial dysfunction and inflammatory responses primarily through oxidative stress and apoptosis. The present study investigated the protective effects of mitoquinol (MitoQ), a mitochondria‑targeted antioxidant, against malathion‑induced toxicity in male Wistar albino rats. A total of 50 rats were divided into the following five groups: i) Control; ii) malathion‑only; iii) malathion + MitoQ; iv) MitoQ‑only; and v) vehicle. Malathion exposure significantly elevated the levels of aspartate aminotransferase, alkaline phosphatase, creatinine, urea and uric acid and decreased total protein, albumin and globulin levels. At the mitochondrial level, malathion reduced antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase and glutathione) and ATP production while increasing reactive oxygen species, leading to oxidative damage. Furthermore, malathion induced upregulation of pro‑apoptotic markers such as Bax, and downregulation of the anti‑apoptotic marker, Bcl‑2. In addition, malathion increased TNF‑α, NF‑κB, Toll‑like receptor (TLR) 2 and TLR4 expression, and malathion toxicity induced severe hepatorenal damage, including vascular congestion, inflammatory infiltration and tubular degeneration. MitoQ co‑administration revealed a trend towards mitigating altered hepatorenal markers, inflammatory markers and regulated apoptotic/antiapoptotic gene markers, with partial restoration in mitochondrial function and histopathological changes. In parallel, MitoQ normalized cellular changes induced by malathion in the liver and kidneys. In conclusion, malathion toxicity in the liver and kidneys is mediated by mitochondrial oxidative stress, apoptosis and inflammation. MitoQ exerts protective effects by restoring mitochondrial homeostasis, reducing inflammatory signaling and mitigating tissue damage. Future research should explore longer treatment durations and potential synergistic effects with other antioxidants to optimize protection against pesticide‑induced toxicity.
View Figures

Figure 1

Effect of MitoQ on hepatic and renal
mitochondrial function in malathion-treated rats. (A) Mitochondrial
SOD activity, (B) GPx activity, (C) ATP levels, (D) GSH levels and
(E) ROS levels in hepatic tissue. renal tissues (F) Mitochondrial
SOD activity, (G) GPx activity, (H) ATP levels, (I) GSH levels and
(J) ROS levels (bottom panel). Data are expressed as the mean ±
standard error (n=10). #P<0.05 vs. malathion + MitoQ,
&P<0.05 vs. Control, MitoQ, and vehicle.
$P<0.05 vs. Control, MitoQ, and vehicle. MitoQ,
mitoquinol; SOD, superoxide dismutase; GPx, glutathione peroxidase;
GSH, glutathione; ROS, reactive oxygen species.

Figure 2

Effect of MitoQ protection on hepatic
and renal mitochondrial biomarkers in malathion-treated rats.
Hepatic (top panel) and renal (bottom panel) levels of (A and E)
cytochrome c, (B and F) TNF-α, (C and G) PGC-1α and (D and
H) TFAM. Data are expressed as the mean ± standard error (n=10).
Statistical analysis was performed using one-way ANOVA followed by
Duncan's multiple-range post hoc test #P<0.05 vs.
malathion + MitoQ, &P<0.05 vs. Control, MitoQ,
and vehicle. $P<0.05 vs. Control, MitoQ, and vehicle.
MitoQ, Mitoquinol; PGC-1α, peroxisome proliferator-activated
receptor γ coactivator 1α; TFAM, mitochondrial transcription factor
A.

Figure 3

Effect of MitoQ protection on hepatic
and renal mRNA expression levels in malathion-treated rats. mRNA
expression levels of Bax in (A) renal and (C) hepatic tissues. mRNA
expression levels of Bcl-2 in (B) renal and (D) hepatic tissues.
Data are expressed as the mean ± standard error (n=10).
#P<0.05 vs. malathion + MitoQ.
&P<0.05 vs. Control, MitoQ, and vehicle.
$P<0.05 vs. Control, MitoQ, and vehicle. *P<0.05
vs. Control.

Figure 4

Effect of MitoQ protection on hepatic
and renal mRNA expression levels of inflammatory markers in
malathion-treated rats. mRNA expression levels of TNF-α in (A)
renal and (C) hepatic tissues. mRNA expression levels of NF-κB in
(B) renal and (D) hepatic tissues. Data are expressed as the mean ±
standard error (n=10). #P<0.05 vs. malathion + MitoQ,
&P<0.05 vs. Control, MitoQ, and vehicle.
$P<0.05 vs. Control, MitoQ, and vehicle.

Figure 5

Effect of MitoQ protection on hepatic
and renal mRNA expression levels of TLR2 and TLR4 in
malathion-treated rats. mRNA expression levels of TLR2 in (A) renal
and (C) hepatic tissues. mRNA expression levels of TLR4 in (B)
renal and (D) hepatic tissues. Data are expressed as the mean ±
standard error (n=10). #P<0.05 vs. malathion + MitoQ,
&P<0.05 vs. Control, MitoQ, and vehicle.
$P<0.05 vs. Control, MitoQ, and vehicle. MitoQ,
Mitoquinol; TLR, toll-like receptor.

Figure 6

Hematoxylin and eosin-stained renal
cortex of different treatment groups. (A) Control group revealed
normal intact glomeruli (indicated with the letter G) and
convoluted tubules (indicated with the letter T). (B) Malathion
group revealed thickening of the glomerular basement membrane
(arrowhead), mesangial expansion (*), vacuolar degeneration of
renal tubules (arrows) and congestion of renal blood vessels
(indicated with the letter C). (C) Malathion + MitoQ group revealed
mild thickening of glomerular basement membrane (arrowhead) and
vacuolar degeneration of renal tubules (arrows). (D) MitoQ group
revealed intact renal glomeruli (indicated with the letter G) and
an accumulation of a proteinaceous substance inside the lumen of
some renal tubules (arrows). (E) Vehicle group revealed intact
renal glomeruli (indicated with the letter G) and vacuolar
degeneration of renal tubules (arrows). MitoQ, mitoquinol.

Figure 7

Hematoxylin and eosin-stained portal
areas of livers of different treatment groups. (A) Control group
demonstrated normal hepatic architecture with polyhedral-shaped
hepatocyte and centrally located nuclei (indicated with the letter
H) and hepatic arteries (indicated with the letter A). (B)Malathion
group revealed severe congestion of hepatic blood vessels
(indicated with the letter C), swelling and macro steatosis of
hepatocytes with nuclear pyknosis (arrowheads) and peri-portal
infiltration of inflammatory cells (arrows). (C) Malathion + MitoQ
group revealed swelling and macro steatosis of hepatocytes with
nuclear pyknosis (arrowheads), and mild increase of fibrous tissue
(indicated with the letter F) in the portal area. (D) MitoQ group
revealed congestion of hepatic blood vessels (indicated with the
letter C) and mild steatosis of some hepatocytes (arrowheads). (E)
Vehicle group revealed congestion of hepatic blood vessels
(indicated with the letter C) and steatosis of hepatocytes
(arrowheads). MitoQ, mitoquinol.

Figure 8

Collective protective impacts of
MitoQ against malathion-induced hepatorenal toxicity. MitoQ,
mitoquinol; SOD, superoxide dismutase; GPx, glutathione peroxidase;
GSH, glutathione; ROS, reactive oxygen species; ALT, alanine
aminotransferase; AST, aspartate aminotransferase; ALP, alkaline
phosphatase; PGC-1α, peroxisome proliferator-activated receptor γ
coactivator 1α; TFAM, mitochondrial transcription factor A.
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Copy and paste a formatted citation
Spandidos Publications style
Althobaiti SA: MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation. Mol Med Rep 32: 296, 2025.
APA
Althobaiti, S.A. (2025). MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation. Molecular Medicine Reports, 32, 296. https://doi.org/10.3892/mmr.2025.13661
MLA
Althobaiti, S. A."MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation". Molecular Medicine Reports 32.5 (2025): 296.
Chicago
Althobaiti, S. A."MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation". Molecular Medicine Reports 32, no. 5 (2025): 296. https://doi.org/10.3892/mmr.2025.13661
Copy and paste a formatted citation
x
Spandidos Publications style
Althobaiti SA: MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation. Mol Med Rep 32: 296, 2025.
APA
Althobaiti, S.A. (2025). MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation. Molecular Medicine Reports, 32, 296. https://doi.org/10.3892/mmr.2025.13661
MLA
Althobaiti, S. A."MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation". Molecular Medicine Reports 32.5 (2025): 296.
Chicago
Althobaiti, S. A."MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation". Molecular Medicine Reports 32, no. 5 (2025): 296. https://doi.org/10.3892/mmr.2025.13661
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